鹿茸促血管新生修复心肌梗死大鼠心肌损伤的实验研究

Cervi Cornu Pantotrichum Repairs Damaged Myocardium of Myocardial Infarction Ratby Promoting Angiogenesis

目的基于血管新生观察鹿茸对心肌梗死(心梗)大鼠心肌损伤的保护效应。方法应用冠状动脉左前降支结扎术建立心梗大鼠模型(假手术组只穿线,不结扎),将50只心梗模型大鼠随机分为模型组、低浓度鹿茸组[100 mg/(kg·d)]、中浓度鹿茸组[200 mg/(kg·d)]、高浓度鹿茸组[400 mg/(kg·d)]、马来酸依那普利组[简称普利组,1 mg/(kg·d)],每组10只。同时设立假手术组10只。各药物干预组分别给予相应药物灌胃,假手术组与模型组每日给予0.5%羧甲基纤维素钠灌胃。4周后采用超声心动图检测大鼠心功能;HE染色观察心肌病理组织学变化;免疫组化法观察心梗边缘区血小板-内皮细胞黏附分子(CD31)与α-平滑肌肌动蛋白(α-SMA)表达;ELISA法检测血清中血管内皮生长因子(VEGF)和成纤维细胞生长因子(bFGF)的含量。结果与假手术组比较,模型组左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)增加,CD31、α-SMA、VEGF与bFGF表达增加(P<0.05,P<0.01),左室射血分数(LVEF)、左室短轴缩短率(LVFS)下降(P<0.01)。与模型组比较,高、中浓度鹿茸组与普利组LVEF、LVFS增加(P<0.01),LVESD、LVEDD降低(P<0.01);高、中浓度鹿茸组心梗边缘区CD31和α-SMA表达增多(P<0.05),血清中VEGF、bFGF含量明显升高(P<0.05)。结论鹿茸通过上调VEGF、bFGF表达,增加微血管密度与小动脉生成,有效促进血管新生,修复心梗大鼠心肌损伤,进而改善心功能。

Objective To observe the protective effect of cervi cornu pantotrichum(CCP)on myocardial damage of myocardial infarction(MI)rat model which is based on angiogenesis.MethodsThe MI rat models were established by ligation of left anterior descending coronary artery.Totally 50 rats were randomly divided into five groups:the model group,the high CCP-dose group(H-CCP,400 mg·kg^-1·d^-1),the medium CCP-dose group(M-CCP,200 mg·kg^-1·d^-1),the low CCP-dose group(L-CCP,100 mg·kg^-1·d^-1)and the enalapril maleate group(EM,1 mg·kg^-1·d^-1),10 in each group.The sham-operation group was also established with 10 rats.The intervention groups were given corresponding dose CCP or enalapril maleate respectively.The sham-operation group and model group were given 0.5%sodium carboxymethyl cellulose.After 4-weeks treatment,cardiac structure and function of rats were assessed by ultrasonic diagnostic apparatus.Pathology changes of myocardial tissues were observed by HE staining.To detect the capillary density and new arterioles in peripheral infarction area,platelet endothelial cell adhesion molecule-1(CD31)andα-smooth muscle actin(α-SMA)were observed by immunohistochemical staining.The level of vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)of serum were detected by ELISA.Results Compared with the sham-operation group,left ventricular end-systolic dimension(LVESD)and left ventricular end-diastolic dimension(LVEDD)in the model group increased(P<0.01).Expressions of CD31,α-SMA,VEGF and bFGF increased(P<0.05),while left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)decreased(P<0.01).Compared with the model group,H-CCP,M-CCP and EM had significant increases of LVEF and LVFS,as well as meaningful decreases of LVEDD and LVESD(P<0.01).The expressions of CD31 andα-SMA obviously increased in the peripheral infarction area of H-CCP and M-CCP(P<0.05).In addition,the level of VEGF and bFGF in rat serum increased significantly(P<0.05).Conclusion CCP could improve the cardiac function of MI rats by up-regulating the expression of VEGF and bFGF which increase capillary density and arteriole formation resulting in the promotion of angiogenesis and repairment of damaged myocardium.